The long-term objective of the research plan contained within this proposal is to elucidate the role of the brainstem circuitry in deglutition. The vagal brainstem complex is responsible for taste-related behaviors such as swallowing, the oral rejection of stimuli, and gagging. The role of metabotropic glutamate receptors (mGluRs) in the transmission of taste-related information has not yet been examined, but our preliminary evidence suggests that mGluR activation inhibits primary afferent transmission within the vagal brainstem complex. mGluR activation also inhibits activity in other systems such as the spinal cord and in aortic baroreceptors via a similar mechanism. Functionally, mGluR mediated inhibition of activity may underlie the habituation of oral stimuli, similar to how mGluRs modulate habituation to odors in olfaction or to painful stimuli in nociception. To study mGluRs in the vagal brainstem complex, I will utilize pharmacological (applications of mGluR agonists and antagonists), patch-clamp electrophysiology, and molecular (PCR, in situ hybridization) techniques to determine the specific role of mGluRs in the processing of vagally mediated taste information. Our experiments may suggest that mGluRs function as presynaptic autoreceptors to decrease the release of glutamate. This could provide a specific mechanism by which habituation to taste stimuli may occur, and these results could extend to two main areas. First, the vagal taste system is important in the gagging reflex for the maintenance of normal air passage. Second, mGluR agonists have recently been shown to decrease lipo-polysaccharide induced anorexia. The understanding of mGluR mediated habituation to oral stimuli in each of these areas may be critical to understanding the conditions. [unreadable] [unreadable] [unreadable]